Childhood precursors of age at first intercourse for females

Age at first intercourse for a sample of adult white women using variables measured during childhood is predicted. Childhood predictors were measured at birth, and ages 5 and 9–11, using existing public-use data on the women. Median age at first intercourse for the sample was 17.5 years. Early family predictors, early developmental characteristics, and temperamental characteristics during childhood together could predict about a fourth of the variance in age at first intercourse. The strongest predictors were motor skills and nightmares at age 5, church attendance with family at age 9, and domineering and mature personality at age 9.This research was supported by grants R01-HD23454 and P30-HD05798 from the National Institute of Child Health and Human Development. An earlier version of this paper was presented at the annual meetings of the Population Association of America, Denver, Colorado, April 30–May 2, 1992.     

Hemoglobin Beth Israel. A mutant causing clinically apparent cyanosis.

We found that an abnormal hemoglobin with a very low oxygen affinity was responsible for overt cyanosis in an otherwise healthy adolescent. Hemoglobin Beth Israel, in which serine replaces the asparagine residue normally present at position 102 (G4) of the beta-polypeptide chain, was associated with normal blood counts and no apparent exercise intolerance in the heterozygous carrier. Cyanosis resulted from a drastically right-shifted oxygen dissociation curve, whose position and shape could account for the absence of "physiologic" anemia. The whole-blood oxygen tension at 50 per cent oxygen saturation was 88 mm Hg (normally 26 +/- 1 mm Hg), and the arterial blood was only 63 per cent saturated with oxygen despite a normal oxygen tension of 97 mm Hg. The hemolysate showed a low oxygen affinity but normal Bohr effect. Unexplained cyanosis, particularly in association with normal arterial oxygen tension should prompt a search for an abnormal hemoglobin, which may obviate the need for invasive diagnostic procedures.     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay.

The fact that certain ultraviolet (UV) filters used in cosmetics display estrogenic activity prompted us to study potential actions on androgen receptors (AR) in the human breast carcinoma cell line MDA-kb2, which expresses functional endogenous AR and glucocorticoid receptors (GR) and is stably transfected with a luciferase reporter plasmid. Dihydrotestosterone (DHT), methyltrienolone (R1881), methyltestosterone, danazol, and androstenedione increased luciferase activity, with EC50 values between 0.11 nM (R1881), 0.14 nM (DHT), and 73.5 nM (androstenedione). DHT-induced luciferase gene expression was inhibited by nonsteroidal antiandrogens, hydroxyflutamide, flutamide, bicalutamide, and vinclozolin. In contrast, the steroidal AR agonist/antagonist cyproterone actetate showed agonistic activity in the absence and presence of DHT, which was not blocked by hydroxyflutamide and thus seems not to be mediated by AR. GR-mediated activation of luciferase by dexamethasone was 100 times less potent than DHT and was not antagonized by hydroxyflutamide. The cell line was used for screening of UV filters, benzophenone-3 (Bp-3), benzophenone-4, 3-benzylidene camphor, 4-methylbenzylidene camphor, butyl-methoxy-dibenzoylmethane, homosalate (HMS), octyl-dimethyl-PABA, and octyl-methoxycinnamate. Two of these, Bp-3 and HMS, antagonized DHT-induced AR activation below cytotoxic concentrations, with IC50 of 5.57 10-6 M (HMS) and 4.98 10-6 M (Bp-3). None of the eight UV filters displayed agonistic activity when tested alone, but high concentrations of Bp-3 induced an increase of luciferase activity in the presence of dexamethasone, which was not blocked by hydroxyflutamide or the estrogen antagonist, ICI 182,780. These data indicate that the UV filters Bp-3 and HMS possess antiandrogenic activity in vitro in addition to estrogenic activity.     

Patients’ and Psychologists’ Preferences for Feedback Reports on Expected Mental Health Treatment Outcomes: A Discrete-Choice Experiment

In recent years, there has been an increasing focus on routine outcome monitoring (ROM) to provide feedback on patient progress during mental health treatment, with some systems also predicting the expected treatment outcome. The aim of this study was to elicit patients’ and psychologists’ preferences regarding how ROM system-generated feedback reports should display predicted treatment outcomes. In a discrete-choice experiment, participants were asked 12–13 times to choose between two ways of displaying an expected treatment outcome. The choices varied in four different attributes: representation, outcome, predictors, and advice. A conditional logistic regression was used to estimate participants’ preferences. A total of 104 participants (68 patients and 36 psychologists) completed the questionnaire. Participants preferred feedback reports on expected treatment outcome that included: (a) both text and images, (b) a continuous outcome or an outcome that is expressed in terms of a probability, (c) specific predictors, and (d) specific advice. For both patients and psychologists, specific predictors appeared to be most important, specific advice was second most important, a continuous outcome or a probability was third most important, and feedback that includes both text and images was fourth in importance. The ranking in importance of both the attributes and the attribute levels was identical for patients and psychologists. This suggests that, as long as the report is understandable to the patient, psychologists and patients can use the same ROM feedback report, eliminating the need for ROM administrators to develop different versions.

     

Distribution of dehydration rates generated by maximal Gardos-channel activation in normal and sickle red blood cells

The Ca(2+)-activated K+ channels of human red blood cells (RBCs) (Gardos channels, hIK1, hSK4) can mediate rapid cell dehydration, of particular relevance to the pathophysiology of sickle cell disease. Previous investigations gave widely discrepant estimates of the number of Gardos channels per RBC, from as few as 1 to 3 to as many as 300, with large cell-to-cell differences, suggesting that RBCs could differ extensively in their susceptibility to dehydration by elevated Ca2+. Here we investigated the distribution of dehydration rates induced by maximal and uniform Ca2+ loads in normal (AA) and sickle (SS) RBCs by measuring the time-dependent changes in osmotic fragility and RBC volume distributions. We found a remarkable conservation of osmotic lysis and volume distribution profiles during Ca(2+)-induced dehydration, indicating overall uniformity of dehydration rates among AA and SS RBCs. In light of these results, alternative interpretations were suggested for the previously proposed low estimates and heterogeneity of channel numbers per cell. The results support the view that stochastic Ca2+ permeabilization rather than Gardos-channel variation is the main determinant selecting which SS cells dehydrate through Gardos channels in each sickling episode.     

Novel risk factors for peripheral arterial disease in young women

PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.